PD-1 (PDCD1)
PD-1 (programmed cell death protein 1) is an immune checkpoint receptor that reduces T-cell activity.
Function
PD-1 is expressed on activated T cells, B cells, and myeloid cells. Its ligands - PD-L1 on tumor and stromal cells, PD-L2 on macrophages - bind PD-1 and recruit phosphatases (SHP-2) that dephosphorylate the T-cell receptor’s signaling intermediates. Antigen-stimulated T cells that receive a PD-1 signal reduce cytokine production, proliferation, and cytotoxicity. Physiologically the system limits collateral tissue damage during infection and maintains peripheral tolerance; chronically stimulated T cells in tumors settle into a PD-1-high “exhausted” state.
In cancer
Tumors up-regulate PD-L1 as an immune-evasion mechanism, one of the escape routes of immunoediting. PD-1-blocking antibodies (pembrolizumab, nivolumab) block this interaction and restore T-cell killing; they produce durable responses in melanoma, lung, kidney, and bladder cancers. The 2018 Nobel Prize recognized this work (Tasuku Honjo, with James Allison for CTLA-4). Response rates are highest in tumors with high PD-L1 expression, high mutation load, and pre-existing T-cell infiltration; resistance arrives through antigen loss, TGF-β-rich stroma, and IL-8-recruited suppressor cells.
Notes
- Human gene symbol: PDCD1; UniProt Q15116; 288 amino acids; CD28 receptor family; two ITIM/ITSM motifs.